Protein docking, the process of predicting the structure of protein-protein complexes, remains a complex challenge in computational biology. While advances like AlphaFold have transformed sequence-to-structure prediction, accurately modeling protein interactions is often complicated by conformational flexibility, where proteins undergo structural changes upon binding. For example, AlphaFold-multimer (AFm), an extension of AlphaFold, achieves a success rate of only 43% in modeling complex interactions, particularly for targets requiring significant structural adjustments. These challenges are especially evident in highly flexible targets, such as antibody-antigen complexes, which are further complicated by sparse evolutionary data. Conventional physics-based docking tools like ReplicaDock 2.0 address some aspects of these issues but often struggle with efficiency and adaptability, highlighting the need for approaches that combine multiple strengths.Researchers at Johns Hopkins have introduced AlphaRED, a docking pipeline that integrates AlphaFolds predictive capabilities with ReplicaDock 2.0s physics-based sampling methods. AlphaRED is designed to address the specific challenges of conformational flexibility and binding site prediction. By leveraging AlphaFold-multimers confidence metrics, such as the predicted Local Distance Difference Test (pLDDT), the pipeline identifies flexible protein regions and refines docking predictions for improved accuracy. For challenging cases like antibody-antigen targets, AlphaRED demonstrates a success rate of 43%, doubling AlphaFold-multimers performance. Additionally, it generates CAPRI acceptable-quality models for 63% of benchmark targets, compared to AlphaFolds 43%. This approach effectively combines the strengths of deep learning and physics-based methods to improve protein complex prediction.Technical Details and BenefitsAlphaRED begins by using AlphaFold-multimer to generate structural templates, which are then evaluated based on interface-specific pLDDT scores. When predictions show low interface confidence, the pipeline employs ReplicaDock 2.0 for global docking simulations, using replica exchange Monte Carlo to explore diverse conformations. For high-confidence models, AlphaRED performs localized refinements, focusing on backbone flexibility in regions indicated by low per-residue pLDDT scores. This targeted approach captures binding-induced conformational changes and improves prediction accuracy. By combining the complementary strengths of machine learning and physics-based sampling, AlphaRED addresses scenarios involving high flexibility or limited evolutionary data more effectively than either approach alone.Results and InsightsAlphaRED was tested on a curated dataset of 254 targets, including rigid, medium, and highly flexible protein complexes. It showed significant improvements across all categories, with notable success in antibody-antigen docking. For instance, AlphaREDs DockQ scores exceeded 0.23 for 63% of the dataset, compared to 43% for AlphaFold-multimer. In blind evaluations like CASP15, AlphaRED excelled, particularly in nanobody-antigen complexes where AlphaFold struggled due to limited co-evolutionary information. Additionally, AlphaRED significantly reduced interface root mean square deviations (RMSDs), refining initial AlphaFold predictions into models closer to native structures. These results suggest that AlphaRED holds promise for applications in therapeutic antibody design and structural biology.ConclusionAlphaRED offers a thoughtful integration of AlphaFolds deep learning capabilities with the adaptive sampling techniques of ReplicaDock 2.0. This pipeline enhances docking accuracy while providing a practical solution for complex cases involving conformational flexibility. Its demonstrated success in challenging docking scenarios, such as antibody-antigen complexes and blind evaluations, makes it a valuable tool for advancing structural biology and drug discovery. By effectively combining the strengths of machine learning and physics-based approaches, AlphaRED represents an important step forward in reliable protein complex prediction and opens new possibilities for research in computational biology.Check out the Paper and GitHub Page. All credit for this research goes to the researchers of this project. Also,dont forget to follow us onTwitter and join ourTelegram Channel andLinkedIn Group. Dont Forget to join our60k+ ML SubReddit. Sana Hassan+ postsSana Hassan, a consulting intern at Marktechpost and dual-degree student at IIT Madras, is passionate about applying technology and AI to address real-world challenges. With a keen interest in solving practical problems, he brings a fresh perspective to the intersection of AI and real-life solutions. Follow us on X (Twitter) to get regular AI Research and Dev Updates here...

Looking for the most recentregular Connections answers? Click here for today's Connections hints, as well as our daily answers and hints for The New York Times Mini Crossword, Wordle and Strands puzzles.Connections: Sports Editionis a mixed bag today. The synonyms are pretty recognizable, but I might not be up on my Australian Open facts. That's a hint, of course. Read on for more hints and answers for today's Connections: Sports Edition puzzle.For now, the game is in beta, which means the Times is testing it out to see if it's popular before adding it to the site's Games app. You can play it daily for now for free and then we'll have to see if it sticks around.Read more: NYT Has a Connections Game for Sports Fans. I Tried ItHints for today's Connections: Sports Edition groupsHere are four hints for the groupings in today's Connections: Sports Edition puzzle, ranked from the easiest yellow group to the tough (and sometimes bizarre) purple group.Yellow group hint: Keep track.Green group hint: Run!Blue group hint: Tennis title-holders.Purple group hint:Not last, but...Answers for today's Connections: Sports Edition groupsYellow group: Numerical record of a game.Green group: Action on the basepaths.Blue group: Australian Open women's single winners.Purple group:First ____Read more: Wordle Cheat Sheet: Here Are the Most Popular Letters Used in English WordsWhat are today's Connections: Sports Edition answers? The completed NYT Connections: Sports Edition puzzle for Jan. 5, 2025. NYT/Screenshot by CNETThe yellow words in today's ConnectionsThe theme is anumerical record of a game. The four answers are outcome, result, score and tally.The green words in today's ConnectionsThe theme is action on the basepaths. The four answers are lead, slide, steal and tag.The blue words in today's ConnectionsThe theme is Australian Open women's single winners. The four answers are Barty, Court, Graf and Osaka.The purple words in today's ConnectionsThe theme is first ____. The four answers are base, down, quarter and take.

Forward-looking: Researchers have achieved a breakthrough in extending the lifespan of EV batteries by adopting a single-crystal electrode design. This innovation not only holds the potential to significantly increase the longevity and range of electric vehicles but also paves the way for more seamless integration of renewable energy sources into power grids. The study, funded by Tesla Canada and the Natural Sciences and Engineering Research Council of Canada, was led by Professor Jeff Dahn from Dalhousie University in Halifax, and a team of researchers. Their innovative battery demonstrated exceptional durability, lasting over 20,000 charge-discharge cycles before reaching the industry-standard 80 percent capacity threshold.To put that into perspective, it equates to powering an EV for an extraordinary 8 million kilometers.The research focused on understanding how internal damage and fatigue accumulate in batteries over time and devising methods to prevent these issues, explained Dr. Toby Bond, a senior scientist at the Canadian Light Source. Using the advanced synchrotron light technology at the University of Saskatchewan, the team conducted detailed analyses of the battery's internal structures.The new single-crystal electrode battery was compared to a conventional lithium-ion battery, which typically lasts around 2,400 cycles before hitting the 80 percent capacity mark. With the CLS's ultrabright synchrotron light, researchers were able to study the internal structures of both battery types without disassembling them, ensuring the integrity of the long-cycled cells was maintained.The results were striking. While conventional batteries exhibited extensive microscopic cracking in their electrode material after repeated charging and discharging, the single-crystal electrode battery showed almost no signs of degradation. "In our images, it looked very much like a brand-new cell," said Dr. Toby Bond. "We could almost not tell the difference." // Related StoriesThe key to this durability lies in the structure of the electrode particles. Traditional batteries use electrodes composed of tiny particles made up of smaller crystal clusters. In contrast, the single-crystal electrode is a single, continuous crystal, making it far more resistant to mechanical stress and strain. Bond likened the difference to that between a snowball and an ice cube the latter being much harder to crush.This breakthrough has far-reaching implications for the EV industry and beyond. Current US regulations require EV batteries to maintain at least 80 percent of their original charge capacity after eight years of operation. However, industry experts are pushing for batteries that last decades, enabling "second-life applications" such as grid-scale energy storage for renewable sources like wind and solar.The extended lifespan of these new batteries could outlast other components of electric vehicles, representing a significant milestone in EV technology. "We really need these vehicles to last as long as possible because the longer you drive them, the better its improvement on the carbon footprint is," Bond explained.The research team reports that these advanced batteries are already in commercial production, with their adoption expected to grow significantly in the coming years. "I think work like this just helps underscore how reliable they are, and it should help companies that are manufacturing and using these batteries to plan for the long term," Bond said.

AI Agents for the Enterprise will be the focus of 2025Lutz Finger"2025 will be the year of the AI agent." Wait didnt we already say that in 2023? Back then, I talked about chaining AI models in my podcast. The excitement around AI was huge, and by 2024, many companies rushed to try generative AI, with some even using chained models. But many of these projects failed to scale. Why? Because they were test projects that were not integrated into the system infrastructure or were missing guardrails and quality controls. This will change in 2025, but the product challenges will remain the same. To see what AI agents can do in 2025, lets consider a simple example: an email-answering tool. Imagine a system that drafts replies to emails automatically. This example shows the opportunities and challenges businesses face with AI agents.Why GPT Wrappers Are Not Enterprise AIThe simplest way to build an email-answering tool is with a GPT wrapper. I saw many of these in 2024. These are basic setups where you connect AI to a small interface. For our use case, this means getting a ChatGPT API key, writing some code to take an email as input, adding a prompt telling the AI what to do, and displaying the response in a clean interface.System Prompt: Answer as if you were Lutz. Lutz always ends his messages with "Cheers!"Input: Hi Lutz, you are invited for dinner on Thursday. Can you come? Cheers, Tim.Output: Thanks, Tim! Let me check my schedule and Ill get back to you soon. Cheers!Even in this simple example, several key challenges emerge for enterprise AI today:No System Integration: The tool cant check my calendar to see if Im free.No Context: It doesnt know if I like Tim or avoid these types of events.No Security: What if the email asks for private details, like my social security number?No Guardrails: How would it handle a controversial question, like asking for political views?No User Control: How much input does the user have in shaping the AIs response?Hallucinations: AI sometimes makes things up, as the warnings on ChatGPT pages constantly remind us: ChatGPT can make mistakes.Large language models are excellent at tasks like summarization or acting as interfaces, but alone they are not enough. As I emphasize in my eCornell certificate program, each of these challenges can be addressed. Lets improve our tool by building AI agents within a workflow.The Workflow of AI Agents: More Than Generative AIAI models can be connected or "chained" to build workflows where the output of one model becomes the input for the next. Think of tools like Zapier or IFTTT, but powered by AI. Instead of fixed steps, the process is dynamic and adapts to each situation. These workflows dont always rely on generative AI like ChatGPT. In fact, they often dontgenerative AI can be too slow and expensive.Heres how this could work for our email tool:Input: Hi Lutz, you are invited for dinner on Thursday. Can you come? Cheers, Tim.System Prompt: Analyze the email and figure out the steps needed to respond.System Output: (1) Check the calendar to see if the user has time. (2) Look up past emails with Tim and previous dinner invites. (3) Predict the chances the user would want to attend based on past behavior. (4) Create three draft replies: one accepting, one declining, and one asking for more details.System Execution: Carry out the outlined steps.Output: Present these three responses to the user.This is how a chained AI model works. It overcomes many of the earlier issues. But the large language model is just one of many tools.MORE FOR YOUAI Agent Workflows: Input - Orchestration - Control - Actions - SynthesizingLutz FingerAll tools need to be integrated and quality-checked. For example, our setup touches on:System Integration: Checking calendars and pulling data isnt AI but requires system connections.Context Search: Using AI to retrieve relevant past interactions (called RAG or Retrieval-Augmented Generation).Traditional AI: Predicting the likelihood of attending uses classic data analysis.User Design: Offering multiple options improves usability and control.In short, its about product workcreating solutions that are reliable and valuable.2025 - AI Agents for the Enterprise2025 will be the year of AI agents. AI will simplify, enhance, or automate workflows across industries. But there wont be one "killer app." If such an app exists, it would likely be Searchsee my prediction on Search. Instead, well see smaller workflows in areas like customer care (see my investment in ultimate.ai), legal support (see flank.io), or sales (see my company, r2decide.com).To build these solutions, engineers and product managers will need to focus on creating value. In my course, Designing and Building AI Solutions, I teach a practical framework for delivering value to enterprise customers in media, finance, healthcare, eCommerce, and other industries:Define the business objective.Collect and clean the data.Develop the agentic workflow.Test with users.Create a feedback loop.This sounds simple, but there are many considerations, including addressing risks such as bias and ethical issues. Most importantly, the focus must remain on value creation. Lets build together.Follow me here on Forbes or on LinkedIn for more of my 2025 AI predictions.

Dynasty WarriorsCredit: KoeiThe Dynasty Warriors franchise is one of those things you either love or find insanely repetitive. I love the warrior-taking-on-waves-of-opponents gameplay, so it has always been a series I give a look when a new version is released.Dynasty Warriors: Origin is on the way, and here are ten things you should know about it, including the release date.Release Date: January 17, 2025As usual, the year is starting off pretty slow with DWO and Donkey Kong Country Returns HD as the biggest releases of January. Gamers who are hungry for some hack-and-slash action might have some interest in DWO.Platforms: PlayStation 5, Xbox Series X|S, and PC via SteamThe newest version of Dynasty Warriors will be available on all current-gen consoles as well as Steam.Developer: Developed by Omega Force and published by Koei TecmoThe original developer and publisher are together for this title, which is the first new entry into the series since Dynasty Warriors 9 in 2018.MORE FOR YOUGameplay: More of the same with new layersDWO maintains the 1 vs. a slew of enemies approach. However, Omega Forces goal in this version was to have 10,000 characters on the screen at once. The idea was to capitalize on the power of the newest consoles. This approach is specifically designed to shine on the PS5 Pro.In addition to hack-and-slash elements, DWO incorporates strategic concepts. Users can issue commands to their troops. Theres also expanded customization for weapons and attacks. Heres a look at gameplay courtesy of a video posted by IGN.Story: The story still focuses on the origins of the Three Kingdoms, but theres a new good guyDWO introduces a new protagonist. The users journey is spiced up by the fact that you have amnesia and interact with historical figures. Im excited to see how that plays out in the game experience.New Features: Bigger armies and better graphicsThe series has run into problems in the past when its tried to reinvent the wheel. DW9 incorporated open-world concepts, and the fanbase didnt seem pleased with that approach.In DWO, youll see a new storyline, characters, the biggest armies in the series history, and improved visuals.Pre-Order Bonuses: Early works soundtrack and a new costume for the protagonistIf you pre-order DWO, youll receive a costume for Wo Long: Fallen Dynasty and an early works soundtrack that includes 191 original tracks from Dynasty Warriors 2 through Dynasty Warriors 9.Early Access: Yes, for the digital deluxe versionCustomers who purchase the Digital Deluxe version of DWO will get 72 hours early access in addition to the pre-order bonuses plus more content. Heres a look at all of the content:Official Book (Digital, Japanese): The digital edition of the official book accessible in-gameOriginal Soundtrack (Digital Edition): Accessible in-gameGold (10,000): Necessary for buying weapons and portable items in the gamePyroxene (30): Necessary for creating gems in the gameCharacter Skill Tree: New techniquesWere not just talking about wardrobe changes. The new protagonist can add new moves, and there is a built-in skill tree for advancement.Reception: Its been good so farFans seem to be pleased with what theyve seen so far. Many are happy that Tecmo and Omega Force are taking things back to the series original approach while attempting to innovate with the story without changing the gameplay altogether.Im looking forward to giving this one a spin toward the middle of the month.

Haiyan Intangible Cultural Heritage Museum / LYCS ArchitectureSave this picture! LYCSJia Xing, ChinaArchitects: LYCS ArchitectureAreaArea of this architecture projectArea:7211 mYearCompletion year of this architecture project Year: 2024 PhotographsPhotographs:LYCS Lead Architects: RUAN Hao, Zhan Yuan More SpecsLess SpecsSave this picture!Text description provided by the architects. Recently, the "Rebirth of Heritage" Yangjianong District Supporting Facilities Project in Haiyan County, Jiaxing City, designed by LYCS Architecture, was officially completed. The project, covering a total area of 7,211 square meters, encompasses diverse functionalities such as exhibition and training spaces, boutique homestays, and commercial facilities.The project includes the Haiyan Intangible Cultural Heritage Museum (referred to as the "Heritage Museum"). The museum's facade renovation incorporates undulating perforated aluminum panels, featuring horizontal lines and vertical elements . Additionally, the project restores the historic "Twin Pools Impression," a renowned scenic feature of Haiyan, and introduces a boutique guesthouse to provide a tranquil retreat.Save this picture!Save this picture!Save this picture!Preserving InheritanceThe former Haiyan Electric Instrument Factory, located at the intersection of Wenchang West Road and Qiyuan Road, is surrounded by key cultural attractions, including Qi Garden, Duwu Garden, Zhang Leping Memorial Hall, and the Haiyan County Museum, making it an ideal location for the ICH Museum.The former site of the Haiyan County Power Meter Factory, established in the 1990s, is a typical small to medium-sized industrial building. The design employs a combination of strategies for revitalization, including "demolition, restoration, preservation, renewal, and integration."Save this picture!Save this picture!Demolishing Temporary StructuresThe site was initially burdened by temporary structures. The design team removed these barriers, widened roads, improved pedestrian and vehicular circulation, and reconnected the site to Qi Garden and the Zhang Leping Memorial Hall, creating a cohesive urban space.Save this picture!Save this picture!Preserving Historical SymbolsThe main buildings are on-site, and their facades are in severe disrepair. The design preserved the industrial aesthetic of the Electric Instrument Factory's original facade while updating its roof and structural elements to facilitate a dialogue between past and present.Save this picture!Save this picture!Revamping FacadesThe new architectural facades adhere to the "dialogue between old and new" principle. Intangible heritage motifs were reinterpreted into contemporary patterns, with ripple-patterned perforated aluminum panels enveloping the structures.Save this picture!Save this picture!Integrating the CorridorNew architectural elements inspired by traditional Haiyan residential styles were introduced at the ground level. A series of continuous pitched roofs echo the vernacular architecture, linking the ICH Museum, historic doorways, and boutique homestays into a cohesive corridor that traverses the site.Save this picture!Save this picture!Save this picture!Restorating Twin Pools Scenic SpotAt the heart of the site lay a pond, the historic location of the Twin Pools Scenic Spot. The design restored this landmark, integrating elements like the Rolling Lantern Dance to craft a dynamic garden landscape, providing a serene setting for both residents and visitors.Save this picture!Project gallerySee allShow lessProject locationAddress:Jia Xing, ChinaLocation to be used only as a reference. It could indicate city/country but not exact address.About this officeLYCS ArchitectureOfficeMaterialsGlassSteelMaterials and TagsPublished on January 05, 2025Cite: "Haiyan Intangible Cultural Heritage Museum / LYCS Architecture" 05 Jan 2025. ArchDaily. Accessed . <https://www.archdaily.com/1025213/inheriting-new-life-haiyan-intangible-cultural-heritage-museum-lycs-architecture&gt ISSN 0719-8884Save? / You've started following your first account!Did you know?You'll now receive updates based on what you follow! Personalize your stream and start following your favorite authors, offices and users.Go to my stream

Lego Fortnite Battle Bus (954 Pieces) $100 See at Amazon See at Best Buy See at Walmart (sold out) Lego Fortnite Peely Bone (1,414 Pieces) $100 See at Amazon See at Best Buy See at Walmart Lego Fortnite Supply Llama (691 Pieces) $40 See at Amazon See at Best Buy See at Walmart Lego Fortnite Durrr Burger (193 Pieces) $15 See at Amazon See at Best Buy See at Walmart Lego's new series of building sets based on Fortnite are now available at major retailers across the US, including Amazon, Walmart, and Best Buy. The Fortnite Lego lineup includes the Battle Bus with a bunch of minifigures, a Peely Bone display model, the Supply Llama, and the Durrr Burger.All four sets initially launched in October as Lego Store exclusives, but now you'll start seeing them on store shelves--as long as they remain in stock, of course. The Fortnite Battle Bus is the No. 1 best-selling new Lego set at Amazon right now, and Walmart is currently sold out of units. It's also worth mentioning that My Best Buy Plus/Total members can save 10% on the new Fortnite Lego sets.Continue Reading at GameSpot

There is a long list of crafting materials to find and use to upgrade your weapons and pod in NieR: Automata. Many of these materials are easier to obtain later in the game, but finding them early can help make your character much stronger earlier on.

Anime is an international phenomenon nowadays, and this development can be at least partially credited to platforms like Crunchyroll. Firmly established as the main option for streaming anime content, the service has an ever-expanding library that covers classics and modern releases, making them as accessible as possible. While not exhaustive, Crunchyroll has the most substantial (legal) selection in the North American market, exceeding both anime-focused and general alternatives. This fact was reinforced by its merger with Funimation, which saw many of the latter's exclusive shows make their way to Crunchyroll.

In most games, players want to explore a world as quickly as possible to reach the end of a dungeon or find a critical NPC in a town. JRPGs are no exception here, especially since players would jump at any excuse to slash their runtime in these lengthy titles considerably.